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Biomedical subjects

B Clarke

Publications and source records attributed to B Clarke.

At least 19 recordsLinked to original sources
PubMed1992

Targeting deletion (homoeologous chromosome pairing locus) or addition line single copy sequences from cereal genomes.

We describe here a protocol for obtaining clones containing sequences present in low copy-number from genomic DNA where moderately and highly repeated sequences predominate. Specific chromosomal regions can be targeted by using deletion or addition line material. We have used this protocol to identify a sequence which has been deleted in both the tetraploid and hexaploid wheat mutants for the homoeologous chromosome pairing locus.

Chromosome Deletion↗
PubMed1992

Stimulation of specific immune responses to simian immunodeficiency virus using chimeric hepatitis B core antigen particles.

Subunit approaches to vaccines against viral diseases have resulted in the development of a number of methods for presentation of defined epitopes to the immune system. We have exploited a highly immunogenic presentation system based on hepatitis B core antigen (HBcAg) particles to produce a number of candidate vaccines against simian immunodeficiency virus (SIV). Recombinant particles have been produced in bacteria which carry multiple copies of defined or predicted neutralizing epitopes of SIV at a number of different sites within the particle. In parallel, a number of synthetic peptide-based SIV vaccines have been produced based on homology to reported neutralizing epitopes in human immunodeficiency virus. Although potent immune responses were elicited against both particulate and peptide forms of the antigen, neutralizing antibodies were not induced as judged by available assays.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Urethral instability.

Urethral instability is still evolving as a clinical entity. Using pressure variation of 15 cm water or more at the point of maximum urethral pressure (MUP), urethral pressure profilometry on patients referred for urodynamic assessment for lower urinary tract symptoms revealed urethral instability in 6.4% of 608 patients. The close association between urethral and detrusor instability was noted. Urethral instability appears to be a cause of frequency and urgency of micturition, and its presence increase the risk of urinary incontinence.

Adult↗
PubMed1991

Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat.

This study evaluated the relationship between the development of fluorescence related to advanced glycosylation end products (AGEs) in the kidney and experimental diabetic nephropathy over a 32-wk period. Control, untreated diabetic, and aminoguanidine-treated diabetic rats were followed for 32 wk with eight weekly measurements of urinary albumin excretion. After 32 wk, collagen-related fluorescence in aorta and kidney (whole kidney, isolated glomeruli, and renal tubules) and glomerular ultrastructure were evaluated. Diabetes was associated with a significant increase in collagen-related fluorescence in the aorta and kidney. Aminoguanidine prevented the increases in collagen-related fluorescence in aorta, isolated glomeruli, and renal tubules but not in whole kidney. Diabetes was associated with increased albuminuria, fractional mesangial volume, and glomerular basement membrane (GBM) thickness. Aminoguanidine attenuated the rise in albuminuria and prevented mesangial expansion without influencing GBM thickness in diabetic rats. The concomitant changes in collagen-related fluorescence, albuminuria, and mesangial expansion with aminoguanidine therapy are consistent with the hypothesis that AGEs may play a role in the development of diabetic nephropathy.

Albuminuria↗
PubMed1990

RS 30026: a potent and effective calcium channel agonist.

1. A series of dihydropyridine derivatives has been evaluated for calcium channel agonist activity using reversal of nisoldipine-induced inhibition of beating of aggregates of embryonic chick myocytes. This test appears to be specific for calcium channel agonists since isoprenaline and cardiac glycosides are inactive. 2. RS 30026 was the most potent of the series, was significantly more potent than CGP 28392 and of similar potency to Bay K 8644 (pEC50 = 7.45, 6.16 and 7.20, respectively). RS 30026 increased edge movement of individual aggregates, in the absence of nisoldipine, by 50% at 2 nM. 3. Compounds were also evaluated for their effects on guinea-pig papillary muscle and porcine coronary artery rings. RS 30026 displayed positive inotropism at concentrations between 10(-9) and 10(-6) M (pEC200 = 8.21), but was a much more powerful inotrope than Bay K 8644, increasing contractility to 1300% of control at 10(-6) M (compared to 350% of control for Bay K 8644). RS 30026 caused vasoconstriction at concentrations between 10(-10) and 10(-7) M. 4. Calcium channel currents in single embryonic chick myocytes were recorded by whole-cell voltage clamp techniques. RS 30026 (100 nM-500 nM) produced large increases in peak current amplitude and shifted the voltage for threshold and maximal currents to more negative values. RS 30026 (500 nM) also produced large increases in the inward tail currents evoked upon repolarization. The effects of Bay K 8644 (50 and 500 nM) were much less marked. 5. Analysis of the activation characteristics of currents showed parallel shifts in the activation curve to more negative potentials in the presence of 50 nm Bay K 8644, with a much smaller shift in the presence of 500nm Bay K 8644. RS 30026 (100 and 500nM) caused concentration-dependent shifts in the activation of the calcium channel currents with an increase of the slope of the curve. 6. RS 30026 appears to be the most potent and effective calcium channel agonist described to date.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1978

Human erythroid burst-forming unit: T-cell requirement for proliferation in vitro.

Human mononuclear leukocytes were fractionated into populations of null, T and B cells by immunoabsorbent column chromatography followed by E-rosette formation and purification of T cells by differential centrifugation and osmotic lysis. The unfractionated and fractionated cell populations were first separately cultured for 14 days in plasma clots in the presence of two international units erythropoietin. Typical erythroid burst-forming unit (BFU-E)-derived colonies grew in the unfractionated cell cultures but not from T- or B-cell cultures. BFU-E colonies grew in null cell cultures but most of the colonies were small and variably hemoglobinized with less than three subcolonies. When intact T cells were added to null cells and cocultured, many typical large BFU-E colonies with more than 10 well homogenized subcolonies appeared. Increasing numbers of large BFU-E colonies in null cell cultures were induced by stepwise addition of T cells but not by the addition of B cells. A conditioned medium in which T cells had been induced to divide by tetanus toxoid substituted for intact T cells in this T-cell-dependent BFU-E colony formation observed in null cells. These findings demonstrate that the BFU-E, a committeded erythroid stem cell, resides in the null cell fraction of peripheral blood, but its proliferative capacity and differentiation in vitro requires a soluble product of T cells. Such experiments now permit a new approach to the assessment of various disorders of erythropoiesis. Erythroid hypoplasia in a particular case may be due to dysfunction of the committed precursor cell or to a failure of a helper effect induced by T cells.

B-Lymphocytes↗
PubMed1978

Studies of globin chain synthesis and globin mRNA content in a patient homozygous for hemoglobin Lepore.

Globin chain synthesis and globin mRNA content were studied in blood cells of a patient homozygous for Hb Lepore. Peripheral blood cells incubated with tritiated leucine synthesized approximately 1.5 to 3% as many Lepore globin chains as alpha chains. Globin mRNA in peripheral blood cell RNA was assayed by molecular hybridization assays using human alpha and beta cDNA, and the results indicated the presence of approximately 1% to 2% as much beta-like mRNA (presumably deltabeta Lepore mRNA) as alpha mRNA. The amount of Lepore deltabeta chain mRNA in peripheral blood cells is therefore proportional to the amount of Lepore globin chain synthesis in the same cells. An incidental observation was the finding that peripheral blood cell RNA of this patient, at a time when she was being heavily transfused, contained substantially higher levels of beta-like mRNA (relative to alpha mRNA) than in subsequent studies. Cell-free translation of this mRNA however revealed that it contained authentic beta chain mRNA which must have been derived in some way from the transfused blood cells.

Child↗
PubMed1976

Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis.

A method for the clonal analysis of murine erythroleukemia cells has been developed which allows the precise characterization of the number of progeny produced by each cell and the degree of differentiation of each progeny cell. The potential of almost every cell in the culture can be monitored because a plating efficiency close to 100% has been achieved. The effects of treatment with an inducer of differentiation (DMSO) on the proliferative capacity of the treated cells have been studied with this technique. Cells from a mass culture treated with inducer give rise to colonies of differentiated progeny when subsequently cloned in the absence of inducer. Colonies exhibiting this phenotype represent the progeny of cells committed to the differentiation pathway by treatment with inducer. We observe that the commitment decision limits the subsequent proliferative capacity of the cell to four additional cell divisions. A quantitative analysis suggests that the commitment decision for each cell is made in a stochastic manner. Irreversible commitment to the expression of differentiated functions occurs with discrete probability per cell generation for many cell generations. The value for this probability is a function of the concentration of inducer (DMSO). A correlative biochemical study suggests that an irreversible commitment decision by a significant proportion of the population precedes or accompanies increases in cytoplasmic globin mRNA levels, one of the earliest detectable biochemical markers for erythroid differentiation in this system. A specific kinetic model based on these considerations has been developed to predict clonal phenotypes as a function of time and probability of commitment. Quantitative predictions based on this model are in excellent agreement with experimental observations. The effectiveness of a stochastic model in predicting the behavior of this system is discussed in relation to the stochastic behavior of normal hematopoiesis and the biochemical mechanisms which control these differentiation programs.

Cell Division↗
PubMed1976

Supergenes in polymorphic land snails. I. Partula taeniata.

The general colour of the shell in Partula taeniata is controlled by at least two loci. One of these (C) has a series of six alleles which determine the yellow (Y) and neutral brown (N) series of colours. Alleles for darker colours are dominant to those for lighter colours, but dominance is not always complete. The pink (P) colours are determined by a second locus (P) which modified the expression of the lighter alleles of the C locus. Orangeshell colour segregates with yellow but its allelic relationship is unknown. Colour of the lip is controlled by a locus (L) with pink lip dominant to white lip. The colour of the spire is determined by a locus (S) with dark (N4) spire dominant to light spire. An intermediate spire colour shows the same pattern of inheritance and may represent the effect of another allele. Banding of the shell is dominant to absence of bands, with two loci (B1 and B2) determining the type of banding. An allele at B1 produces the frenata pattern; an allele at B2 produces zonata; together they produce lyra. All the loci for which linkage data are available are linked so strongly that the whole array may be considered a supergene. Self-fertilisation takes place primarily during early reproductive life. About 20 per cent of the young of the first mating of an individual are produced by selfing, but over the whole reproductive span the frequency is only about 2-5 per cent. There is inconclusive evidence for heterozygote advantage of banded individuals.

Alleles↗
PubMed1976

Supergenes in polymorphic land snails. II. Partula suturalis.

The colour and banding of the shell of Partula suturalis are controlled by a single locus (M) with a series of at least six alleles. MX, giving apex as a homozygote, is dominant to MF1, giving frenata, which is dominant to the other alleles. MF2 is similar to MF1 except in its relation with MA. MF2MA produces bisecta and provides a striking example of a heterozygote that is qualitatively different from both homozygotes for the alleles producing it. MA gives atra as a homozygote and is dominant to MC and MS. MC, giving cestata as a homozygote, is recessive to all except MS. MS, giving strigata, is the universal recessive. It is suggested that the locus may be complex. The direction of coiling of the shell is determined by the H locus with HS (sinistrality) dominant to HD (dextrality). The expression of coiling is delayed by one generation, the maternal genotype determining the phenotype of the offspring. M and H are not linked. Self-fertilisation occurs infrequently and non-randomly.

Alleles↗
PubMed1976

Infection in the intensive care unit.

An epidemic of infection associated with Serratia marcescens and other Gram-negative organisms resistant to aminoglycosides and other chemotherapeutic agents occurred in the Intensive Care Unit, and spread to other areas of the hospital. This paper describes the problems of sepsis in the critically ill patient, outlines the occurrence of organisms in the patients concerned in this epidemic, and discusses the policies adopted to control the incidence of life-threatening infection caused by bacteria resistant to all other agents.

Anti-Bacterial Agents↗